HLA Polymorphism in Israel 8. The Armenian Community in Jerusalem

Gene and phenotype frequencies for the three HLA loci were determined for 90 random Armenians from the Old City of Jerusalem. Relatively high frequencies were found for HLA-A2, A3 and Aw24, while the lowest frequencies were those for Aw23 and Aw25. The major distinguishing antigen, when compared with European Caucasoids is Bw35 with a frequency of 22%. Two unusual associations between the B and C loci were observed: Bw 17, Cw3 and B7, Cw3. Another interesting association in Armenians, Aw32 Cw4, has previously been found only among Cochini Jews and Malay populations.     

Bu and SV: Two Closely Related B-Locus Specificities

The B15/Bw21/Bw35 related specificities 'Bu'and 'SV'have been studied in Bristol and in Leiden, both independently and with mutually exchanged sera and cells. Evidence is presented that these specificities are likely to be discrete though very closely related antigens occurring with a combined phenotype frequency of about 1% in Dutch and English Caucasians. SV may be associated with Aw36, while no clear-cut haplotype or phenotypic association has yet emerged for Bu with any HLA–A or C locus antigen. Bu and SV appear to be related to the variant of B15 reported to be common in Negroid populations.     

HLA antigens and different clinical forms of 21-hydroxylase deficiency in the French population

HLA associations with 21-OH deficiency were studied on respectively 109 and 60 congenital and late onset French index cases. Significant negative associations were found with antigens B8: congenital forms; B5, DR3: late onset. Significant positive associations were observed with A3, Bw47 (A3 Cw6 Bw47 DR7): congenital forms; B40: salt-wasting form; B5: simple virilizing form; Aw33, B14, DR1, DR2, DRw6 (Aw33 B14 DR1): late onset form. Among late onset patients not bearing B14 antigens significant positive associations were observed with B12 and B35.     

HLA in two islands of French Polynesia

The HLA-A, B, and C antigens of 243 individuals from two Polynesian islands, Maiao and Hiva Oa, have been characterized. 328 haplotypes were defined by family analysis. Most frequent antigens were A2, A11, Aw24, A26 , Aw34 ; Bw38, Bw39 , Bw48 , Bw55 , Bw56 , Bw60 ; Cwl, Cw3, and Cw4. Several other antigens were present at low frequency or were present on only one island. New variants of Bw22 and B40 were found. Despite an overall similarity in antigens of the two islands, the combination of HLA-A, B and C antigens on the haplotype were distinctive. Of 328 total haplotypes identified, 65 were unique. Thirteen of these (20%) were present on both islands. Twenty-eight (43%) were unique to Hiva Oa and 24 (37%) were unique to Maiao . Significant, positive linkage disequilibrium values (delta) for HLA-A, B and HLA-B, C antigens were also different for the two populations.     

HLA in Buerger's disease

Recent studies have focused on the possible genetic factor(s) in the pathogenesis of Buerger's disease as well as in Takayasu's disease. We investigated HLA-A, B, C, DR, and DQ antigens in 59 patients with Buerger's disease to confirm statistically significant high frequencies of Aw24, Bw40, Bw54, Cw1, and DR2 antigens and a low frequency of DR9 and DRw52 as compared with those in 152 normal Japanese individuals. As the haplotpye Aw24-Bw54-Cw1-DR4 is known to be common among Japanese, a significantly high frequency of haplotype Bw54-DR2 found in cases of Buerger's disease, instead of that of Bw54-DR4, may suggest a possible cross-linkage occurrence in chromosome 6, which could prove to be an important causative phenomenon in the pathophysiology of Buerger's disease.     

The HLA antigen distribution in the gipsy population in Hungary

A group of Gipsies living in two distinct geographic areas in Hungary was determined for HLA-A,B,C,DR antigens during the 8th Histocompatibility Workshop. A quite strange distribution of HLA antigens was found after comparing the data to those of Hungarian population. HLA-A1, Bw52, Bw22, B40, Cw1, DR2 and DRw8 are significantly increased in Gipsies, while A3, B7, B12, Cw3, DRw6 and DR7 are decreased. The strongest gametic associations were determined between the allele pairs A1/Bw61, A2/Bw52, Bw22/Cw1, DR2/Bw52 and DRw8/B40. Some deviations from the Hungarian controls were detected in the distribution of the blood groups too. Specifically, the incidence of Rh/D/ negativity and Gm/2/factor positivity is much lower and the incidence of Gm/1/ factor positivity is much higher than in the control Hungarian population. These differences between Gipsy and Hungarian populations indicate their different ethnic origin, and suggest the Middle-Eastern roots of the Gipsy population.     

Biochemical HLA typing: a population study in 112 Caucasians

In order to define frequencies and associations of biochemically defined HLA-A and -B specificities and their variants and subtypes in a Caucasian population, biochemical HLA typing was performed in a panel of 112 Austrians. Already known rare variants of HLA-A2, A3, A30, Aw33 and B39 and the more frequent subtypes of HLA-B27, B35, B44 and, in addition, a so far unknown variant of HLA-B18 were present in the panel. Family segregation analyses of the biochemically defined HLA class I variants revealed that they could be found only in certain rare haplotypes, most of them in high linkage disequilibrium. The basic variant of HLA-A30, for example, obviously occurred only in the HLA-A30, B49, Cw7 haplotype, similar to the Aw33 acidic variant, which was exclusively found in the Aw33, Bw58, Cw3 haplotype. None of the biochemical variants was found in frequent common haplotypes.     

HLA Polymorphism in Israel: 4. Israeli Jews originating from Rumania

The frequencies of 29 HLA antigens of the A amd B loci were studied in 130 Israeli Jews originating from Rumania. The antigens A1, A2, Aw19 and B14, Bw16 and Bw35 occurred with the highest frequencies. The most common haplotypes were (A1, B17), (Aw26, Bw16) and (A28, Bw22). These results are similar to those observed in Polish and Russian Jews.     

HLA-A,B,C, Bf and glyoxalase I polymorphisms in a sample of the kabyle population (Algeria)

HLA (A,B and C) gene and haplotype frequencies were determined in 44 Berber families from the Kabyle tribe. The Bf and Olo polymorphisms were also defined and the haplotypes were deduced from these family data. The main association (A1, B8, BfS; A29, B12, GIo²; Aw33, B14, BfS, GIo¹; Cw5, B18, BfF1; A1, Bw17) showed the relationship between the populations from the southwest of Europe, and this population. Another association, A11 and Bw21, was found also in Twareg, which are probably of the same origin.     

A Comparison of HLA Data of the North American Black with African Black and North American Caucasoid Populations

For purposes of genetic comparison, the available HLA data on United States and African Black, together with United States Caucasoid populations, are summarized. Antigen frequencies and pairwise linkage disequilibria are presented for the HLA-A, -B and -C loci in Black populations typed for the 1975 Histocompatibility Testing Workshop. The Black population samples comprise 356 North American Blacks and 411 African Blacks of whom 222 were Bantu. These are compared with a sample of 503 American Caucasoids. All significant linkage disequilibria between the A and B loci found in North American Blacks were also present in the North American Caucasoids. Between the B and C loci, Bw35 and Cw4 were in strong linkage disequilibrium in all groups. Significantly stron association between the A and C loci (Aw28 with Cw3) were observed only in the African Blacks. There were unique disequilibria both in the American Caucasoids and African Blacks. Although the frequencies of many antigens in U.S. Blacks lie between those in Africans and U.S. Caucasoids, there are exceptions such as Aw33, Bw35, Cw4.     

Histocompatibility Determinants in Israeli Jewish Patients with Coeliac Disease: Population and Family Study

The association between HLA and coeliac disease (CD) was studied in the Jewish population of Israel. A total of 112 patients were typed for HLA-A,B,C antigens, including 67 patients whose families were typed in order to deduce the genotypes. Forty-seven patients were typed for HLA-DR antigens. The HLA-A,B,C data show a pattern of association, which is similar to that found in European CD patients: HLA-B8 is increased, although to a lower degree; a suggestive, insignificant increase for Aw30, B13 and Cw6 and a decrease of Bw35 were noted. The DR antigens DR3 and DR7 are associated with CD in the Jewish population. An excess of DR3/DR7 heterozygotes was noted. The data from family and population studies support a model in which two different HLA-DR associated genes are intereacting.     

HLA-A and B antigens in AKA pygmies

HLA-A and B antigens were studied in 543 AKA pygmies. The present analysis showed two characteristics of this pygmoid group: the absence of HLA-A1, A11, B8 and Bw38 and the high frequency of Aw30, B17, B27, B37, B40 and Bw39. The strongest gametic associations were found with the haplotypes Aw30, B37 and A3, B5.     

HLA Polymorphism in Israel: 3. Ashkenazi Jews of German Descent

Seventy-three random Jewish individuals whose families have lived in Germany for at least 4-5 generations, were typed for HLA antigens at the A and B loci. In comparison with other European populations, the frequencies of B7 and B12 are low whereas Bw35 is almost twice as frequent (21%). Among the uncommon associations found in the German Jews were: (A2, Bw21), (Aw25, B18), (A29, B14), (A28, Bw15). The frequent haplotype (Aw24, Bw35) was previously found, but only in Asia and in American Indians. Subdivisions of the subjects according to geographic regions within Germany point to differences in gene frequency between the groups.     

HLA disease association and protection in HIV infection among African Americans and Caucasians

In a previous investigation, we demonstrated an increased progression of overt AIDS in the African American population compared to the Caucasian population as reflected by the significantly lower absolute number of CD4+ lymphocytes detected in the African American population in an earlier study. The present study elucidates some of the possible genetic factors which may contribute to disease association or protection against HIV infection. The HLA phenotypes expressed as A, B, C, DR and DQw antigens were revealed by the Amos-modified typing procedure. NIH scoring was utilized to designate positive cells taking up trypan blue. A test of proportion equivalent to the chi 2 approximation was used to compare the disease population (n = 62; 38 African Americans, 24 Caucasians) to race-matched normal heterosexual local controls (323 African Americans, 412 Caucasians). Significant p values were corrected for the number of HLA antigens tested. HLA markers associated with possible protection from infection for African Americans were Cw4 and DRw6, whereas Caucasians expressed none. Disease association markers present in the African American population were A31, B35, Cw6, Cw7, DR5, DR6, DRw11, DRw12, DQw6 and DQw7, whereas in the Caucasian population A28, Aw66, Aw48, Bw65, Bw70, Cw7, DRw10, DRw12, DQw6 and DQw7 were demonstrated. The highest phenotypic frequency for a disease association marker in the study was for HLA-DR5 (62.9%) in the HIV-infected African American population without Kaposi's sarcoma compared to a frequency of 28.9% for the regional control group (p = 0.0012). We conclude that genetic factors do have a role in HIV infection since only 50-60% of those exposed to the AIDS virus will become infected.     

Study of HLA system in a Mataco population:

A search for antigens of the HLA system has been carried out in 53 Mataco Indians of Argentina living in a geographically isolated area in the northeast of the country. Samples were mostly collected from adults of both sexes who were not directly related.
Lymphocyte typing was performed using the microcytotoxicity technique of NIH. 118 sera specific for 15 antigens of the first HLA locus, 22 antigens of the second and 6 of the third were used.
The most frequently found alleles were HLA-A28, Aw31 and A2 for the first locus; B15 and B40 for the second; and Cw3 and Cw4 for the third.
In addition to previously published investigations on South American Indians, our typing work shows a remarkable homogeneous gene pool and a restricted range of polymorphism; therefore, a further set of haplotypes rendered us also restricted. The most frequent haplotypes that showed a significant statistical linkage desequilibrium were: A2-Cw4, A28-Bx, A2-Cw3, Aw31-Bw16, Aw24-Cw3, B15-Cw3, Bw16-Cw3 and A28-B5.
Some of these haplotypes have also been found in other indian populations.     

The HLA system in the Korean population

The frequencies of HLA-A, B, C, DR, and DQ antigens, HLA-D (HTC-defined) haplotypes, and the HLA-linked genetic markers glyoxalase I (GLO), factor B (Bf), C2 and C4 were studied in 162 healthy unrelated Koreans. Antigens A2, A24, A26, B44, B51, Bw62, B35, Cw1, Cw3, DR2, DR4, DRw6, DR7, and DRw8 were observed at frequencies of 15% or greater, and GLO-2, BfS, C4A*3, C2C, C4A*4, C4B*1, and C4B*2 were also frequently observed. The antigens A23, A25, B18, Bw42, Bw47, and B21 were not observed at all. HLA-DR4 was the most common class II antigen and was associated with a series of HLA-D-defined haplotypes including Dw4, Dw10, Dw13, and Dw15. The HLA-DRw6, DR2,Dw8, and DRw8 haplotypes were also found frequently. DR2 haplotypes were either Dw2 or Dw12, while all DRw8 haplotypes tested corresponded to the DB7 or Dw "8.3" specificity that has been described in other Oriental populations. Significant linkage disequilibrium was found between the alleles A2,Cw1; A30,B13; A30,Cw6; A30,DR7; Cw1,Bw22; Cw5,B12; Cw6,B13; Cw6,DR7; B7,DR1; B12,Dw6; B12,DR7; B12,Dw7; B13,DR7, B17,DR3; Bw22,C4B*6; DRw6,BfF; and C4A*4,C4B*2. A comparison of gene frequencies and commonly observed haplotypes between Koreans, Chinese, Japanese, and Caucasians showed that while Koreans share several characteristics in common with other Oriental populations, there are allelic frequencies and haplotypes in Koreans that are distinct.     

HLA Polymorphism in Israel: 2. Israeli Jews originating from Russia

HLA typing of 123 Israeli Jews of Russian origin showed a high frequency for HLA— A1, A2, Aw19 and B14, Bw16 and Bw35 of the A and B loci, respectively. The most frequently occuring haplotypes were ( A1, B17 ), ( Aw25, B18 ), ( Aw26, Bw16 ), ( Aw19, B13 ), ( Aw23, B5 ) and ( Aw25, Bw35 ). This study reveals a striking resemblance in the distribution of frequencies of HLA alleles and haplotypes between Russian Jews and two other East European Jewish communities (presented in this issue) of Polish and Rumanian origin.     

The HLA-B12 and -B40 cross-reactive groups and their serological relationships

The serological analysis of 82 broad HLA-B antisera, produced by pregnancy alone, containing reactivity against HLA-B 12 and/or B40 positive cells and up to nine additional specificities was performed, using highly selected lymphocyte panels. The HLA typing of 76 of the antiserum donors and 75 of their husbands showed that the antisera were stimulated in response to one of 10 different HLA-B antigens. It also showed the influence of serum donor HLA-B antigens on the reaction range of the antiserum produced, as well as significant HLA-B antigen frequency disturbances within varous groups of the antiserum donors. Fifteen HLA-B specificities were found to comprise the B12 cross-reactive group and its related cross-reactions, with bidirectional cross-reactivity occurring between Bw44, Bw45, Bw49 and Bw50 (unidirectional between Bw44 and Bw50). Seventeen specificities were observed in the B40 cross-reactive group and its related crossreactions, with bidirectional cross-reactivity occurring between Bw41, Bw50, Bw60 and Bw61. Antisera were studied that showed: (1) cross-reactivity between Bw44, Bw45 and Bw60 stimulated antisera and both subdivisions of the B12 and B40 antigens; (2) cross-reactivity between B13, Bw44, Bw49, Bw60 and Bw61 stimulated antisera and Bw47; and (3) cross-reactivity between Bw44, Bw49, Bw60 and Bw61 stimulated antisera and B13, with bidirectional cross-reactivity occurring between B13, Bw60 and Bw61 and between B13 and Bw44. Bidirectional crossreactivity was also observed between B37 and Bw44 and between B7 and Bw60. HLA-Bw48 was shown to be included within the reaction range of both B7 and Bw60 stimulated antisera. Preferential cross-reactivity with one of two antigen subdivisions was extensively observed and occurred exclusively between antigens of the same Bw4/Bw6 association as the antiserum stimulating specificity. The results are discussed within the framework of the existence of multiple shared antigenic determinants.     

The Genetic Control of HLA-A and B Antigens in Somatic Cell Hybrids: Requirement for β2 Microglobulin

The lymphoblastoid cell line Daudi lacks both HLA—A and B antigens and β₂ microglobulin. Somatic cell hybrids derived from a fusion between this line and D98/AH-2 were shown to express four HLA antigens not detectable on either parent cell, A1, A10(Aw26), Bw16(Bw38, Bw17. The initial definition by direct cytotoxicity assay was confirmed by absorption of reactions against target T lymphocytes, thus avoiding problems due to contaminating Ia antibodies, and by blocking the reactions by pretreatment with a chicken anti-human β₂ microglobulin serum. That the new specificities were due to the Daudi HLA region was confirmed by the finding that interspecific hybrids between Daudi and A9L, containing a single human chromosome 6, expressed A10 and Bw17. This also defined the haplotypes of Daudi as A10(Aw26), Bw17 and A1, Bw16(Bw38).
The re-expression of the Daudi HLA—A and B antigens in two independent sets of hybrids indicates that it does not carry a mutation in the HLA region. It has previously been reported that somatic cell hybrids with Daudi, which contain chromosome 15, do not express human β₂ microglobulin. These results suggest that the reason for the lack of HLA—A and B antigens on Daudi is a secondary effect due to the mutation(s) in the β₂ microglobulin gene.     

HLA Polymorphism in Israel

One hundred and twenty three Iraqi Jews, now living in Israel, were studied for their HLA polymorphism. Gene frequencies exceeding .1 were found for A1, A3, Aw19, B5, B12, and Bw35. A28, B8 and B14 were relatively rare whereas Aw25 and Bw37 were not found at all. Significant gametic associations occurred for (Aw23, Bw21), (Aw26, Bw16), (A11, B5), (A28, B8) and (A28, B7). The Iraqi Jewish population was found to be typical of Asiatics and Middle Easterners.